Limited Small-Cell Lung Cancer: A Potentially Curable Disease

Limited Small-Cell Lung Cancer: A Potentially Curable Disease

The article by Sherman et al is a broad review of the recent
developments in the treatment of patients with small-cell lung cancer
who present with limited disease. Intially, the authors emphasize
that the increasing use of more intensive and refined staging
procedures, such as computed tomography (CT) scan and, more recently,
positron-emission tomography (PET) scan, have resulted in stage
migration. This phenomenon has led to improved outcomes of both
limited and extensive disease, but has not necessarily improved
overall survival.

Further refinement of staging is expected with the use of various
monoclonal antibodies to identify tumor cells in bone marrow or to
detect occult micrometastasis in lymph nodes by a reverse
transcriptase polymerase chain reaction. The prognostic value of the
detection of small numbers of tumor cells in the bone marrow has
recently been demonstrated by Pasini et al.[1] In addition, we can
expect an increased use of magnetic resonance imaging (MRI) in the
detection of brain metastases.

Advances in Treatment

With respect to treatment, emphasis is placed on the importance of
the combined use of combination chemotherapy with chest irradiation
and prophylactic cranial irradiation. In particular, the issue of
timing of the treatment modality with chemotherapy is also discussed.
I can only agree with the authors that with respect to optimal timing
of thoracic radiation, no firm conclusions can be drawn at present.

Highly encouraging are the results of using twice-daily chest
irradiation combined with cisplatin (Platinol) and etoposide,
resulting in a 5-year survival of 26% compared to 16% with chest
irradiation given once daily. Confirmation of these results is
needed, because neither Bonner et al[2] in the North Central Cancer
Treatment Group (NCCTG) study nor Mennecier et al[3] from France have
been able to produce similar results.

These differences in results may be attributed to variations in the
study design. The Bonner study used a break in the delivery of
thoracic irradiation at approximately the midperiod of the
radiotherapy schedule, whereas Turrisi et al[4] did not use such a
break. The NCCTG study also used chest irradiation at an earlier
stage (chemotherapy cycle 1 or 2) than the Turrisi study (cycle 4 or
5). Finally, the thoracic irradiation field was different, with the
NCCTG study encompassing only the postchemotherapy tumor volume in
the field. The latter resulted in less toxicity but was perhaps
associated with a higher failure rate. In the French study,
differences in the results might exclusively be a question of patient
selection, with the French study including more patients with poor
prognostic factors.

Regarding local treatment, it should be remembered that a small
proportion (5%) of patients with small-cell lung cancer present with
stage I or II disease. For this group, surgery followed by
chemotherapy is indicated, which yields a 5-year survival rate of 25%
to 70%. This is similar to the result for nonsmall-cell lung
cancer patients presenting with the same stage.[5]

The combination of etoposide and cisplatin is the most commonly used
chemotherapy regimen and, in most countries, the one considered to be
the standard treatment for limited disease when administered together
with radiotherapy. The authors statement that a combination of
carboplatin (Paraplatin) and etoposide might be equally effective was
recently challenged at the 9th World Conference on Lung Cancer in
Tokyo, September 2000.[6] A total of 34 patients received etoposide,
120 mg/m² intravenously (IV) on days 1, 3, and 5, and
cisplatin, 100 mg/m² on day 1. The other 34 patients received
the same dose of etoposide and carboplatin, 400 mg/m² on day 1.
The median survival was 15 months vs 10 months (P < .05).

Promise of Newer Agents

As mentioned by the authors in this article, real progress in the
treatment of small-cell lung cancer has been modest during the last
20 years, and the development of new cytostatic agents with activity
against resistant cells is needed. In the 1990s, a series of new
agents were tested, such as the taxanes (paclitaxel [Taxol] and
docetaxel [Taxotere]) and topoisomerase I inhibitors (topotecan
[Hycamtin] and irinotecan [Camptosar]). Among these, irinotecan
appears especially promising.

In a two-armed Japanese study with 77 patients in each arm, the
median survival and 1-year survival rate were 411 days and 56% in the
irinotecan/cisplatin arm vs 282 days and 34% in the
etoposide/cisplatin arm (P = .00025 for survival, one-sided
log-rank test).[7] Further studies with irinotecan and the other new
agents are awaited with interest.

In addition to the positive development of new classical cytostatic
agents, it is encouraging to note that ongoing testing of
metalloproteinase inhibitors and tumor-tailored gene therapy is
taking place. These are all attempts to increase the present cure
rate for the most devastating of all pulmonary carcinomas: small-cell
lung cancer.